You might not realize it, but there's a really good chance that you have taken an enzyme inhibitor in your lifetime. About 40 to 50% of antibiotics, antivirals, many other kinds of drugs work by inhibiting the activity of enzymes. There are two main types of enzymatic inhibitors. So one type is called a competitive inhibitor.
This is where the inhibitor will compete for the active site of an enzyme. And then there are non-competitive inhibitors, and this is where an inhibitor binds to a different site on the enzyme. The competitive inhibitors are the easy ones to understand, so we're going to do those first.
This is a picture of competitive inhibition. So we have our enzyme here and our substrate. You can see the substrate fits nicely into the binding pocket of the enzyme, the active site.
And if you... have a competitive inhibitor and it binds to this enzyme, what it does is it prevents the substrate from binding. Kind of like when you come home and your cat or your dog is in your chair, right?
You can't sit down because there's already an animal there. So a competitive inhibitor works a lot like this. And there are some important competitive inhibitors in microbiology. A famous one is the drug sulfanilamide.
And it... if you take a look at sulfanilamide and compare it to this molecule para-aminobenzoic acid, I hope you'll notice that the whole bottom half of the molecule is identical. And it turns out that bacteria use para-aminobenzoic acid as part of the process of making folic acid, and bacteria require folic acid to grow.
And because these two structures are so similar, if you give a bacteria sulfanilamide, it will prevent the... their ability to make folic acid. So this is a nice diagram of the whole process.
Here is para-aminobenzoic acid, and you can see there are several enzymatic steps, and ultimately the product folic acid is necessary for bacteria to make DNA, to make RNA, and to make protein. There's actually two antibiotics that block this pathway. There's another one called trimethoprim, and it also is a competitive inhibitor. of the enzyme dihydrofolate reductase. So you have two different drugs, both functioning at different parts of this pathway as competitive inhibitors.
And they're actually often prescribed together because with both of them, they're quite effective in killing antibiotics and preventing their growth. Sulfa drugs have been around for a really long time and they're very inexpensive. You see them used quite a bit in, particularly in countries that are poor, where the cost of drugs are prohibitive. And so these are...
have been around, they're way off patent, and they're inexpensive and easy to access. Okay, I said non-competitive inhibition was more complex, so let's talk about that. On the face of it, it's not so bad. So here's our enzyme here, and with a non-competitive inhibitor, the inhibitor is binding to a site other than the active site.
So you can see this is where the substrate would normally bind, but we have a non-competitive inhibitor bound. and it binds to something called an allosteric site. In fact, a lot of people call non-competitive inhibitors allosteric inhibitors, so you might hear me use that term interchangeably. When the allosteric inhibitor binds, what happens is it changes the three-dimensional shape of the enzyme, and now the substrate no longer fits. And so basically, it's a switch.
It shuts off the enzyme by preventing it from binding substrate. And some non-competitive inhibitors are... reversible and some are irreversible.
So an example of an irreversible non-competitive inhibitor is cyanide. It binds to the enzyme cytochrome C oxidase, which is a key component of the electron transport chain. And when cells are exposed to cyanide, it shuts down cellular respiration.
And so cyanide is a potent poison for that reason, because most aerobic organisms require the electron transport chain in order to make enough energy to survive. So it usually is causes death fairly fast and in a fairly grisly way as well. Cells actually use non-competitive inhibition to control metabolic pathways. So this is actually pretty interesting and it's a little bit complex, so bear with me as we go through this.
Here's an enzymatic pathway. You can see it's got three enzymes, enzyme 2 and enzyme 1, enzyme 2, and enzyme 3. And this is the product and this is the starting material. so the substrate.
And let's go through the pathway to product. So we've got our enzyme one and then another step here. And then ultimately, we end up with this end product.
Let's say that over time this pathway has been operating kind of like a, let's say it's a hat factory, right? We have starting materials, we're making hats, and pretty soon we've made so many hats that we need to stop the production of our hats. Okay, so it can be a hat factory, it can be a chemical factory, but here's our molecule. Essentially, these end products build up, whether you're building hats or you're building this particular molecule that the cell needs. Somehow the cell needs to be able to turn off this first enzyme.
It needs to shut it down so that it doesn't keep making this product until the cell needs more of it. Because there's no sense making something you don't need. That's costing the cell energy.
So this end product, you can see that one of the things it can do is it can come over here and here's our same enzyme, but do you see that now we have a lot of this end product and some of it is bound to the allosteric site of this enzyme and it's a... non-competitive inhibitor. When it binds it changes the shape and now our substrate no longer fits. So over here when the allosteric site was open we had the pathway was allowed to run but over here with the path with this allosteric inhibitor in place the pathway has been shut down. Now what happens after the cell uses up all of these end products then the site will become free again and the pathway can get can start up.
So this is the cells way of controlling this path. When it has a lot of the end product, the pathway will shut down so it doesn't keep making something it doesn't need. When it runs out of the end product, it will fall out of the active site, and now this pathway can commence. So this is called feedback inhibition. If you've taken physiology, I'm sure you've heard the term, but this is a mechanism of feedback inhibition.
So basically the end product is providing feedback. to this pathway to say whether or not the pathway should continue to operate or whether it should be shut down. It's a little bit like, you know, a manufacturing plant manufacturing hats, right?
And once there's enough hats that they have plenty to sell, they're going to stop making them. They'll focus on doing something else. And then when you start running out of hats, you're going to scramble to make more so that you have enough to sell.
So it's very similar, I think, to thinking about how a manufacturing line would operate in a plant. All right, so our last lecture slide set is going to be on redox reactions in metabolism and the production of ATP.